Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mapping enzymatic catalysis using the effective fragment molecular orbital method: towards all ab initio biochemistry.

ABSTRACT: We extend the Effective Fragment Molecular Orbital (EFMO) method to the frozen domain approach where only the geometry of an active part is optimized, while the many-body polarization effects are considered for the whole system. The new approach efficiently mapped out the entire reaction path of chorismate mutase in less than four days using 80 cores on 20 nodes, where the whole system containing 2398 atoms is treated in the ab initio fashion without using any force fields. The reaction path is constructed automatically with the only assumption of defining the reaction coordinate a priori. We determine the reaction barrier of chorismate mutase to be [Formula: see text] kcal mol(-1) for MP2/cc-pVDZ and [Formula: see text] for MP2/cc-pVTZ in an ONIOM approach using EFMO-RHF/6-31G(d) for the high and low layers, respectively.

SUBMITTER: Steinmann C

PROVIDER: S-EPMC3625203 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Mapping enzymatic catalysis using the effective fragment molecular orbital method: towards all ab initio biochemistry.

Steinmann Casper C Fedorov Dmitri G DG Jensen Jan H JH

PloS one 20130412 4

We extend the Effective Fragment Molecular Orbital (EFMO) method to the frozen domain approach where only the geometry of an active part is optimized, while the many-body polarization effects are considered for the whole system. The new approach efficiently mapped out the entire reaction path of chorismate mutase in less than four days using 80 cores on 20 nodes, where the whole system containing 2398 atoms is treated in the ab initio fashion without using any force fields. The reaction path is ...[more]

PMID: 23593259

Similar Datasets

Polarized Molecular Orbital Model Chemistry. I. Ab Initio Foundations.

Project description:The objective of this paper is to examine the minimal requirements for obtaining semiquantitative polarizabilities of molecules, in order to provide a well-founded starting point for a new semiempirical molecular orbital formulation that is more suitable than presently available methods for simulating electronic polarization effects. For this purpose, we present polarizability calculations for 38 molecules with 36 basis sets, including many unconventional ones, and five semiempirical molecular orbital theories based on neglect of diatomic differential overlap. We conclude that two basis sets are particularly promising to serve as bases for semiempirical improvement, namely STO-3G(,P), in which diffuse p functions are added to all hydrogens, and 3-(21,3,21)G in which a minimal basis set is augmented with one extra s function on every atom. We especially recommend the former because all intra-atomic overlap integrals are zero by symmetry, which makes it a better candidate for neglect-of-differential-overlap treatments.

| S-EPMC3518311 | biostudies-literature

Comparative Binding Analysis of Dipeptidyl Peptidase IV (DPP-4) with Antidiabetic Drugs - An Ab Initio Fragment Molecular Orbital Study.

Project description:Dipeptidyl peptidase IV (DPP-4) enzyme is responsible for the degradation of incretins that stimulates insulin secretion and hence inhibition of DPP-4 becomes an established approach for the treatment of type 2 diabetics. We studied the interaction between DPP-4 and its inhibitor drugs (sitagliptin 1, linagliptin 2, alogliptin 3, and teneligliptin 4) quantitatively by using fragment molecular orbital calculations at the RI-MP2/cc-pVDZ level to analyze the inhibitory activities of the drugs. Apart from having common interactions with key residues, inhibitors encompassing the DPP-4 active site extensively interact widely with the hydrophobic pocket by their hydrophobic inhibitor moieties. The cumulative hydrophobic interaction becomes stronger for these inhibitors and hence linagliptin and teneligliptin have larger interaction energies, and consequently higher inhibitory activities, than their alogliptin and sitagliptin counterparts. Though effective interaction for both 2 and 3 is at [Formula: see text] subsite, 2 has a stronger binding to this subsite interacting with Trp629 and Tyr547 than 3 does. The presence of triazolopiperazine and piperazine moiety in 1 and 4, respectively, provides the interaction to the S2 extensive subsite; however, the latter's superior inhibitory activity is not only due to a relatively tighter binding to the S2 extensive subsite, but also due to the interactions to the S1 subsite. The calculated hydrophobic interfragment interaction energies correlate well with the experimental binding affinities (KD) and inhibitory activities (IC50) of the DPP-4 inhibitors.

| S-EPMC5104442 | biostudies-literature

Interaction of HIV-1 aspartic protease with its inhibitor, by molecular dynamics and ab initio fragment molecular orbital method.

Project description:For the three complex crystal structures of HIV-1 aspartic protease (an enzyme of AIDS) with its inhibitor in the Protein Data Bank, molecular dynamics of the generalized Born surface area and the ab initio fragment molecular orbital of an ABINIT-MP calculation was performed to obtain the binding free energy, the molecular orbital energy, the interaction energy of residues with an inhibitor and the charge transfer at the active site. The inhibitors are five symmetric cyclic ureas, of which three were modelled, and an asymmetric dipeptide. The interaction energy of the inhibitor at the active sites of aspartic acid is as great as 50 kcal mol(-1), coinciding with a tetrahedral transition state. For the inhibitor with a higher affinity, charge was transferred to the inhibitor from the active site. The difference in symmetry of the inhibitor was not evident. Binding free energy corresponds to the experimental value of the binding constant, while molecular orbital energy does not always, which is considered to be an entropy effect.

| S-EPMC2394819 | biostudies-literature

Fragment-Based Ab Initio Molecular Dynamics Simulation for Combustion.

Project description:We develop a fragment-based ab initio molecular dynamics (FB-AIMD) method for efficient dynamics simulation of the combustion process. In this method, the intermolecular interactions are treated by a fragment-based many-body expansion in which three- or higher body interactions are neglected, while two-body interactions are computed if the distance between the two fragments is smaller than a cutoff value. The accuracy of the method was verified by comparing FB-AIMD calculated energies and atomic forces of several different systems with those obtained by standard full system quantum calculations. The computational cost of the FB-AIMD method scales linearly with the size of the system, and the calculation is easily parallelizable. The method is applied to methane combustion as a benchmark. Detailed reaction network of methane reaction is analyzed, and important reaction species are tracked in real time. The current result of methane simulation is in excellent agreement with known experimental findings and with prior theoretical studies.

| S-EPMC8197069 | biostudies-literature

Toward optimal fragment generations for ab initio protein structure assembly.

Project description:Fragment assembly using structural motifs excised from other solved proteins has shown to be an efficient method for ab initio protein-structure prediction. However, how to construct accurate fragments, how to derive optimal restraints from fragments, and what the best fragment length is are the basic issues yet to be systematically examined. In this work, we developed a gapless-threading method to generate position-specific structure fragments. Distance profiles and torsion angle pairs are then derived from the fragments by statistical consistency analysis, which achieved comparable accuracy with the machine-learning-based methods although the fragments were taken from unrelated proteins. When measured by both accuracies of the derived distance profiles and torsion angle pairs, we come to a consistent conclusion that the optimal fragment length for structural assembly is around 10, and at least 100 fragments at each location are needed to achieve optimal structure assembly. The distant profiles and torsion angle pairs as derived by the fragments have been successfully used in QUARK for ab initio protein structure assembly and are provided by the QUARK online server at http://zhanglab.ccmb. med.umich.edu/QUARK/.

| S-EPMC3551984 | biostudies-literature

Ab initio structure solution of a proteolytic fragment using ARCIMBOLDO.

Project description:Crystal structure determination requires solving the phase problem. This can be accomplished using ab initio direct methods for small molecules and macromolecules at resolutions higher than 1.2 Å, whereas macromolecular structure determination at lower resolution requires either molecular replacement using a homologous structure or experimental phases using a derivative such as covalent labeling (for example selenomethionine or mercury derivatization) or heavy-atom soaking (for example iodide ions). Here, a case is presented in which crystals were obtained from a 30.8 kDa protein sample and yielded a 1.6 Å resolution data set with a unit cell that could accommodate approximately 8 kDa of protein. Thus, it was unclear what had been crystallized. Molecular replacement with pieces of homologous proteins and attempts at iodide ion soaking failed to yield a solution. The crystals could not be reproduced. Sequence-independent molecular replacement using the structures available in the Protein Data Bank also failed to yield a solution. Ultimately, ab initio structure solution proved successful using the program ARCIMBOLDO, which identified two α-helical elements and yielded interpretable maps. The structure was the C-terminal dimerization domain of the intended target from Mycobacterium smegmatis. This structure is presented as a user-friendly test case in which an unknown protein fragment could be determined using ARCIMBOLDO.

| S-EPMC6130419 | biostudies-literature

Towards fully ab initio simulation of atmospheric aerosol nucleation.

Project description:Atmospheric aerosol nucleation contributes to approximately half of the worldwide cloud condensation nuclei. Despite the importance of climate, detailed nucleation mechanisms are still poorly understood. Understanding aerosol nucleation dynamics is hindered by the nonreactivity of force fields (FFs) and high computational costs due to the rare event nature of aerosol nucleation. Developing reactive FFs for nucleation systems is even more challenging than developing covalently bonded materials because of the wide size range and high dimensional characteristics of noncovalent hydrogen bonding bridging clusters. Here, we propose a general workflow that is also applicable to other systems to train an accurate reactive FF based on a deep neural network (DNN) and further bridge DNN-FF-based molecular dynamics (MD) with a cluster kinetics model based on Poisson distributions of reactive events to overcome the high computational costs of direct MD. We found that previously reported acid-base formation rates tend to be significantly underestimated, especially in polluted environments, emphasizing that acid-base nucleation observed in multiple environments should be revisited.

| S-EPMC9568664 | biostudies-literature

Proposal of novel natural inhibitors of severe acute respiratory syndrome coronavirus 2 main protease: Molecular docking and ab initio fragment molecular orbital calculations.

Project description:This paper proposes natural drug candidate compounds for the treatment of coronavirus disease 2019 (COVID-19). We investigated the binding properties between the compounds in the Moringa oleifera plant and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 using molecular docking and ab initio fragment molecular orbital calculations. Among the 12 compounds, niaziminin was found to bind the strongest to Mpro. We furthermore proposed novel compounds based on niaziminin and investigated their binding properties to Mpro. The results reveal that the introduction of a hydroxyl group into niaziminin enhances its binding affinity to Mpro. These niaziminin derivatives can be promising candidate drugs for the treatment of COVID-19.

| S-EPMC8084281 | biostudies-literature

Effective Reconstruction of Expectation Values from Ab Initio Quantum Embedding.

Project description:Quantum embedding is an appealing route to fragment a large interacting quantum system into several smaller auxiliary "cluster" problems to exploit the locality of the correlated physics. In this work, we critically review approaches to recombine these fragmented solutions in order to compute nonlocal expectation values, including the total energy. Starting from the democratic partitioning of expectation values used in density matrix embedding theory, we motivate and develop a number of alternative approaches, numerically demonstrating their efficiency and improved accuracy as a function of increasing cluster size for both energetics and nonlocal two-body observables in molecular and solid state systems. These approaches consider the N-representability of the resulting expectation values via an implicit global wave function across the clusters, as well as the importance of including contributions to expectation values spanning multiple fragments simultaneously, thereby alleviating the fundamental locality approximation of the embedding. We clearly demonstrate the value of these introduced functionals for reliable extraction of observables and robust and systematic convergence as the cluster size increases, allowing for significantly smaller clusters to be used for a desired accuracy compared to traditional approaches in ab initio wave function quantum embedding.

| S-EPMC10210252 | biostudies-literature

Ab initio calculations of conduction band effective mass parameters of thermoelectric

Project description:Since there are still research interests in the physical properties of quasi-binary thermoelectric

| S-EPMC7529947 | biostudies-literature